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Immunoglobulin V H ‐gene usage of autoantibodies in mercuric chloride‐induced membranous glomerulopathy in the rat
Author(s) -
Dammers Peter M.,
Bun Judy C. A. M.,
Bellon Blanche,
Kroese Frans G. M.,
Aten Jan,
Bos Nicolaas A.
Publication year - 2001
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2001.01231.x
Subject(s) - isotype , microbiology and biotechnology , antibody , epitope , immunoglobulin class switching , biology , autoantibody , laminin , antigen , monoclonal antibody , chemistry , immunology , b cell , genetics , cell
Summary Brown‐Norway (BN) and Dorus Zadel Black (DZB) rats develop a T‐cell‐dependent membranous glomerulopathy (MGP) with high proteinuria and antiglomerular basement membrane (GBM) autoreactive antibodies (Abs), upon exposure to mercuric chloride (HgCl 2 ). Laminin is an important autoantigenic target of the anti‐GBM Abs, absorbing ≈ 30% of the anti‐GBM reactivity. Although many anti‐GBM Abs have undergone isotype switching, it is currently unclear whether affinity maturation occurs during the HgCl 2 ‐induced autoimmune response. To address this question we analysed the rearranged immunoglobulin heavy chain variable‐region genes (V H DJ H regions) of 15 mAbs that were previously obtained from HgCl 2 ‐treated rats. Seven of these mAbs exhibit reactivity towards laminin. Our study showed that the V H ‐gene usage of antilaminin mAbs is largely restricted to the PC7183 V H ‐gene family (six out of seven). In addition, we demonstrated that at least three out of six laminin reactive and five out of six non‐laminin‐binding mAbs are encoded by germline V H genes (a total of eight out of 12 mAbs). Of the eight mAbs that are encoded by germline V H genes, seven are of a non‐immunoglobulin M (IgM) isotype, indicating that isotype switching has occurred in these mAbs in the absence of somatic mutations. The mutations observed in the V H genes of the four remaining mAbs do not provide strong evidence for antigenic selection. The data support the notion that B cells in this model of MGP are not subjected to affinity maturation and probably result from polyclonal B‐cell activation.